The model works in a controlled space: one target, one molecule, known conditions, and a dataset that defines what "good" looks like. A living body is not that space. A drug taken into the body must survive the stomach, cross into the bloodstream, avoid being broken down by the liver, reach the right tissue, and act on the target without disrupting the many other processes that resemble it. The body also contains thousands of other molecules, enzymes, and cell types that can interact with the drug in ways the model never represented.
This is why the same molecule can score well and behave badly. The model measured it against a target in isolation. The body measures it against everything at once. The diagram places the two environments side by side so the missing layers are visible: the model's clean target-and-molecule view on one side, and the body's layered reality — absorption, distribution, metabolism, excretion, immune response, and off-target interactions — on the other.